Herbal pharmacology and Drug interaction of TCM Dr. Baisong Zhong M.D(China), Ph.D, L.Ac. WWW: Painandacupuncture.netfirms.com E-mail: [email protected].

Herbal pharmacology and Drug interaction of TCM

Dr. Baisong Zhong M.D(China), Ph.D, L.Ac.

WWW: Painandacupuncture.netfirms.comE-mail: [email protected]

Preface

In 2002, sales of herbs/botanical supplements increased to an estimated $4.3 billion per year

From 2001 to 2003, herbal products for women increased by approximately 25%

In 2005, a secondary analysis of the complementary and alternative medicine (CAM) supplement to the 2002 National Health Interview Survey (NHIS)2,3 estimated that more than 38 million Americans use herbs and dietary supplements. More recent estimates have placed this number as high as 60 million.

http://nccam.nih.gov

Chapter 1 Introduction to Pharmacology of TCM

 1.Concept of Pharmacology of TCMPharmacology of TCM is the study of the actions, usage, mechanism

and adverse effects of TCM (includes acupuncture, herbs, qigong, tui-na, TCM theory, etc.) with modern scientific methods.

2. Tasks of Pharmacology of TCM

(1)   Research the functions of TCM

(2)   Research how TCM acts on the human body

(3) Research why TCM has those functions

In this course, we will only be studying the herbal pharmacology of TCM. (HTCM)

3. History and Development of HTCM4. Research Methodology of HTCM

(1)   To analyze the chemical structures of TCM herbs, and to purify the active structures or even to synthesize them. Then, to put them into clinical trials methodically after understanding their pharmacology and toxicology

(2)   To research HTCM according to the theory of TCM      i. To explain the crux of TCM according to formula theory      ii. To research TCM syndromes through animal experiments.      iii. To research the behaviors, characteristics and properties of

the herbs in complex TCM formulas. iv. To help discover new patent herbs or formulas                      

Research Methodology of HTCM

in vitro studies

animal studies

clinical studies

 5 Tastes of HTCM (1)   Pungent Herbs   i. Herbs that relieve exterior syndrome: They mainly contain volatile oils that o       Promote sweating o       Improve microcirculation o       Are anti-bacterial o       Are anti-viral exterior syndrome o       Stimulate appetite o       Relax spasm o       Relieve pain

      ii.      Herbs that regulate qi:

They mainly contain volatile oils that o       Regulate digestive function o       Activate smooth muscle o       Help secretion of digestive juice o       Stimulate appetite o       Relax spasm o       Relieve pain

(2)   Sweet HerbsMost of them are rich in nutrition (amino acid, sugar, glycoside).

Some of them can improve immune function.(3)   Bitter HerbsThey are rich in alkaloid and glycoside that are anti-

bacterial, anti-viral and anti-inflammatory (Huang Lian has

berberine).(4)   Sour HerbsThey are rich in tannic acid and organic acids that have

strong astringent action.(5)   Salty HerbsThey contain iodine and inorganic salts.

 6. Acute Toxic Test of HerbsLethal Dose 50 or LD 50 is determined and defined as

that dose of a drug which kills 50%of the animals to which it is administered. The concept of LD50 suggests that if a whole population (rather than just an experimental sample) were exposed to this dose (which is actually the median lethal dose), 50% of the population would live and 50% would die.

 7. Long Term Toxic Test of Herbs – about half a

yeare.g. Chuan Wu and Ma Qian Zi have toxic effect on the

heart, and Mu Tong, and Guang Fang Ji have toxic effect on the kidney.

Chapter 2 Herbs that Relieve Exterior Syndromes

Properties of HRES1. Inducing sweating2. Abating fever(1)   Induce sweating(2)   Dilate blood vessels of skin(3)   Decrease cAMP in brain(4)   Disturb the synthesis of prostaglandin E(5)   Is anti-inflammatory(6)   Treat the cause of fever by means of anti-bacteria3. Having analgesic action

4.Regulating immune function and anti-inflammation

5.Being anti-anaphylaxis

6.Being anti-bacterial and anti-viral

7.Having anti-tissue and expectorant action, and anti-asthma action

Questions?

What kinds of actions do the 5 tastes have?

     Ma Huang (Ephedra)[Main Components]1.      L-ephedrine2.      D-pseudo-ephedrine[Effects & HTCM]1. Inducing sweating(1)   Reduce sweat gland’s ability to re-absorb sodium (Na+,

increases the crystal osmotic pressure) and thus increase sweating(2)   Stimulate CNS and a receptor( )2. Relieving asthma

(1)   Stimulate adrenergic nerve to release adrenaline

(2)   Lead to a rise in intraccelluor cAMP levels, make subsequent bronchial smooth muscle relax

(3)   Prevent to release powerful inflammation mediators

3. Inducing diuresis

(1)   Dilate potassium ion (K+) channel of renal tubule and improve blood circulation

(2)   Prevent renal tubule from re-absorbing sodium

4. Having anti-inflammatory and anti-allergenic reaction

5.Stopping cough and expectorating

6.Reducing fever, being anti-bacterial and anti-viral

7.Exciting CNS

8. Stimulating heart & increasing blood pressure(11)

[Indications]

1. Bronchial asthma

2. Stuffy nose

3. Low blood pressure

4. Urticaria.

[Side Effects]1. Lead to bleeding of eyes

2. ON nervous and cardiac system(eg:MDMA, CRYSTAL METH 、 CRYSTAL 、 SHABU 、 GLASS 、 BASE. Eg:Nervousness, anxiety, palpitations, headaches, nausea, hypertension, seizures, strokes, myocardial infarction, hyperthermia, and death have been reported. )

3. Lead to restlessness, insomnia

[Interaction]

1. avoid with medication that are for lowing blood pressure 2. avoid with medication that are for promoting sweats

Adverse Effects

1.Nervousness, anxiety, palpitations, headaches, nausea, hypertension, seizures, strokes, myocardial infarction, hyperthermia, and death have been reported.

2.Myocardial ischemia and infarction, dysrhythmias, and uncontrolled hypertension have been reported following consumption of ephedra

3.This may be caused by increased oxygen demand of the myocardium in persons with pre-existing arteriosclerotic heart disease who ingest this substance

4.Reports of cerebral vascular ischemia, intracranial hemorrhage, and central nervous system vasculitis have all been reported in association with the ingestion of ephedra. Seizures have also been associated with its use. Ephedra extracts have been shown to be toxic to specific neuronal cell lines.

5.Acute psychosis has been linked with ephedra usage.

Gui Zhi (Cinnamon twig, cinnamomun)

[Main Components]

1. cinnamic aldehyde

2. cinnamic acid

3. phenylpropyl acetate (few)

[Effects & HTCM]

1. Dilating blood vessels to promote sweating

Cinnamic aldehyde can help blood flow to skin, especially with ephedra

2. Reducing fever & stopping pain

This action is related to promoting sweating.

It can increase the ability of enduring pain(pain threshold).

3. Tranquilizing: can anti- convulsion.

4. Being anti-inflammatory and anti-allergic

5. Being anti-bacterial (staphylococcus aureus, pneumococcus) and anti-viral (influenza virus)

It can be anti-staphylococcus aureus, anti-TB. It can be anti-ECHO11 (V.). [Indications] [Side Effects]

   Chai Hu (Bupleurum Root)

It is bitter in flavor, slightly cold in nature, and acts on liver and gallbladder

[Main Components]

1. Saiko-side a, b, c and d

2. a-spinastral

3. Volatile oil

4. Fatty acid

[Effects & HTCM]

1. Abate fever. The dosage size of bupleurum root is directly proportional to its effectiveness in lowering

fevers due to typhoid bacillus and colibacillus. Saiko-side and volatile oil have the fever abating effect.

2.Tranquilize, has analgesic effect, and stop cough. The saiko-side has this effect but is less potent than codeine.

3.Promote immune function. It can strengthen the action of Kupffer’s cell and NK cell.

4.Protect liver, cholagogize (benefiting the gallbladder) and lower cholesterol. The saiko-side has this effect. Bupleurum root prepared with vinegar is more effective in lowering cholesterol (especially for triglyceride)

5.Treat digestive ulcer. The saiko-side can prevent the mucosa of the stomach from being impaired by acid and alcohol.

6.Relax the spasm of intestinal muscles.

[Indications] TCM1. Alternate fever and chills2. Hypochondriac pain3. Irregular menstruation4. Prolapse of uterus Pharmacology1. Respiratory infection.2. Cough due to different lung diseases3. Viral Hepatitis4. Hypercholesterolemia [Side Effects]1. Excessive intake would lead to sleepiness, poor appetite,

and abdominal distention. 2. Injection may lead to allergic reaction.

Interactions Interactions with Drugs (1)Bupleurum may increase the risk of bleeding when taken with drugs that

increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners")

such as warfarin(Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal, anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

(2)Bupleurum may stimulate the adrenals and may decrease the effects of antihypertensives(drugs for high blood pressure). Patients taking blood pressure medications, including beta-blockers or ACE inhibitors, should use cautiously.

(3)Although not well-studied in humans, bupleurum may reduce cholesterol levels. Caution is advised in patients taking cholesterol-lowering agents.

(4))Bupleurum may increase the amount of drowsiness caused by some drugs. Examples include benzodiazepines such as lorazepam (Ativan®) or diazepam (Valium®), barbiturates such as phenobarbital, narcotics such as codeine, some antidepressants, and alcohol.

Ge Gen (Kudzu)

Kudzu originated in China and was brought to the United States from Japan in the late 1800s. It is distributed throughout much of the eastern United States and is most common in the southern part of the continent.

Kudzu has traditionally been used in China to treat alcoholism, diabetes (high blood sugar), gastroenteritis (inflamed stomach or intestine), and deafness.

Evidence suggests kudzu may improve signs and symptoms of unstable angina (chest pain), improve insulin resistance, and have a positive effect on cognitive function in postmenopausal women. However, most studies have suffered from methodological weaknesses and small sample sizes.

Chinese healers have used kudzu to treat high blood pressure and chest pain and to minimize alcohol cravings. Research indicates that puerarin (a constituent of kudzu) may increase blood flow to the heart and brain which helps explain certain traditional uses.

   Ge Gen (Kudzu, pueraria) [Main Components]1. Daidzin2. Daidzein3. Puerarin [Effects & HTCM]1. Reducing fever.2. Effects on circulatory system (1)   Puerarin can reduce blood pressure (2)   Promote the circulation of the brain (3)   Dilate the coronary vessels. It can relax the spasm of

coronary vessels. Good for coronary heart diseases. (4)   Promote heart function.

3. Relax the smooth muscles of the intestines

4. Other actions: (1)   It can reduce the function of platelets (2)   It can lower blood sugar [Indications]

1. Hypertension

2. Coronary Heart Diseases

3. Migraines [Side Effects]

1. Side Effects and Warnings Currently, there are no side effects reported of kudzu treatment when taken by

mouth. Intravenous puerarin has caused intravascular hemolysis (destruction of red blood cells). Intraperitoneal administration of puerarin or crude extracts of Pueraria lobata caused hypothermia (low body temperature).

In theory, intraperitoneal administration of puerarin or crude extracts of Pueraria lobata may cause hypothermia. Kudzu root may also cause weight loss, although this has not been well studied in humans.

2. Interaction: Antidiabetics: Anticoagulant & antiplatelet drug:

3. Pregnancy & BreastfeedingKudzu is not recommended in pregnant or breastfeeding women due to a lack of

available scientific evidence.

Chapter 3 Herbs that clear Heat Syndrome   Properties of herbs that clear heat syndrome  1. Anti-microbial. (1)   Anti-bacterial and also eliminate bacterial toxin

(e.g. gram-positive Staphylococcus and gram-negative Colibacillus)

(2)   Anti-viral (e.g. Influenza virus)2. Anti-toxin (1)   Decrease the endotoxin of gram-negative bacteria. (2)   Anti-bacterial exotoxin `

3. Anti-pyretic (abating fever) The action is related to the anti-microbial and anti-

toxin properties of the herbs.4. Effects on immune function Some of the herbs increase the WBC and their

phagocytic function. (e.g. Huang Lian, Huangqin). Some of them restrain the phagocytic function.

5. Anti-inflammation6. Anti-cancer7. Expelling free radicals: the free radicals are

related to age and cancer.  Examples of herbs that clear heat syndrome

Huang Lian (Coptis root)“Huang Lian can do no right, Ren Shen can do no

wrong”[Main Components]1. Berberine2. Coptisine3. Worenine4. Palmatine[Effects and HTCM]1. Anti-microbes2. Anti-toxin3. Anti-pyretic (abate fever)4. Effects on immune function

5. Effects on cardiovascular system (1)   Reduce ventricular arrhythmia,

ventricular fibrillation and atrial flutter. (2)   Promote cardiac contractility. (3)   Reduce heart rate (4)   Lower blood pressure (especially good

for diastolic pressure)6. Prevent platelet adhesion7. Lower blood sugar, anti-cancer (for

leukemia)

[Indications]1. Hypertension2. Supra-ventricular arrhythmia3. Dysentery4. Acute Enteritis5. Cholecystitis6. Respiratory tract infection7. Diabetes [Side Effects] Little1. A few suffer from allergic reactions (drug rashes)2. Gastrointestinal effects: fullness, nausea, vomiting

Berberine

Huang lian root contain berberine 5-7%

Berberine and its relative derivatives show antidiarrhtic , antimicrobial, anticancer, antiinflammatory and antiarrhythmic et al

Berberine

Berberine is a bitter-tasting, yellow, plant alkaloid.

It is present in the roots, and stem bark of various plants

Berberine has also been used historically as a dye, due to its yellow color.

Berberine Activity

Antimicrobial Cardiovascular effects Anti-inflammatory effect others

Antimicrobial Effects

Bacterial Diarrhea Intestinal Parasites Ocular infections Et al

Bacterial Diarrhea

Direct antibacterial effects Inhibiting the intestinal secreatory response

cause by V. cholerae, and E. coli Also block the adherence of bacterial to

erythrocytes and epithelial cells Clinical studies showed that a single dose of

berberine sulfate 200-400mg orally significantly reduced liquid diarrhea stool compare to control without side effects (Rabbani et al 1987; 1996)

Dosage and toxicity

The LD 50 of berberin in mice 25mg/kg iv. ; while no gross toxic effects in dog at 45 mg/kg

High doses may result in lowered BP, dyspnea, flu-like symptoms, GI discomfort and cardiac damage

The therapeutic dose of berberine as oral supplement is typically 200 mg two or three times daily

pharmacokinetics Sulfate-conjugated metabolites of berberine were

identified after oral administration at 0.9 g per day, 3 days, in healthy volunteers' urine.

Little berberine was recovered in urine compared with its metabolites (Pan et al., 2002 ).

Berberine seems to be extensively metabolized in the body.

there is little information available on pharmacokinetics following administration. .

Huang qin

Scutellaria baicalensis Georgi Has antioxidant, antiviral, antibacterial,

antiinflammatory, antiallergic, and sedative properties.

Major components are flavonoids, such as baicalin, baicalein, wogonin et al, dominated by baicalin, which makes up 12-17% of the root

Baicalein

Baicalein, one of the major flavonoids contained in the dried roots, possesses a multitude of pharmacological activities.

Baicalein and dosage In China, baicalin is prepared in injection form for rapid action.

The dosage is 60-120 mg of baicalin intramuscularly, 1-2 times per day; or a daily IV drip containing 500-1200 mg may be utilized for more severe diseases.

Orally, Huangqin is given in decoction, with dosages of about 6-12 grams per day, yielding baicalin in amounts of 1-2 grams.

Baicalein tablets, and highly purified baicalein extracts in powder form (with 95% flavonoid content) are used at doses of 1-2 grams per day. These treatments are usually for acute syndromes; lower doses of baicalin in complex formulas would be utilized for prolonged therapy.

Pharmacokinetics

Baicalin orally, slow absorbed, take 7-16 hrs to the peak concentration

im, quick absorb, takes 0.4 hrs to peak concentration, half time about 0.6 hrs

Kidney excretion

Baicalin activity

Inhibition of infections (especially respiratory tract viral infections).

Anti-inflammatory (e.g., for asthma or atopic dermatitis) Inhibition of cancer cell proliferation; Protecting bone marrow and promoting hemopoiesis during

cancer therapies and protecting the intestines from adverse chemotherapy effects;

Blood pressure lowering Sedative, Bile-secreting, Neuroprotective and hepatoprotective

Inhibition of infections

Antibacterial and antiviral agents. They are effective against staphylococci, cholera, dysentery, pneumococci and influenza virus.

especially respiratory tract viral infections anti hepatitis B virus. Both Huangqin and

isolated baicalin are widely used in China for treatment of viral hepatitis and are believed to have potent protective action against liver fibrosis caused by viral activity.

Formula

Shuanghuanglian (SHL for short) is a modern formula

extracts of three herbs: lonicera (shuanghua, often called jinyinhua), scute (huangqin), and forsythia (lianqiao). (2:1:1)

treatment of respiratory tract infections, cases of viral myocarditis et al.

Anti-inflammatory

Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibition in a dose-dependent manner

Prostaglandin E2 generation was inhibited

for asthma or atopic dermatitis

Huang qin

anti - histamine effect: huang qin possesses antihistamine effect. It can inhibit edema of rats model.

anti allergenic effect: alcohol extract of huang qin inhibits acute asthma attack and allergenic eczema.

Baicalein inhibits permeability of capillaries and anti acetylcholine and anti anaphylaxis effects.

Anti-tumor

Inhibition of cancer cell proliferation Induction of apoptosis by baicalin was accompanied with

the marginal generation of intracellular reactive oxygen species (ROS), the increase of the cytochrome c, and the disruption of mitochondrial transmembrane potential prior to the activation of caspase-3.

On the other hand, baicalin showed little toxic effect on peripheral blood mononuclear cells from healthy volunteers.

These results indicate that baicalin acts as a prooxidant and induces apoptosis via mitochondrial pathway.

Antioxidants

Antioxidants play a key role in cardiovascular disease, cancer, cataract formation, the aging process, inflammatory diseases, and a whole variety of neurological disorders.

Inflammation and cancer

Chronic infection and inflammation contribute to about 25% of all cancer cases worldwide

Anti-tumor

Flavones (chrysin, baicalein, and galangin), flavanones (naringenin) and isoflavones (genistein, biochanin A) inhibit the activity of aromatase (CYP19), thus decreasing estrogen biosynthesis and producing antiestrogenic effects, important in breast and prostate cancers.

Others

Protecting bone marrow and promoting hemopoiesis during cancer therapies and protecting the intestines from adverse chemotherapy effects;

lowers blood pressure

Plant-derived baicalein and its analogs are used to treat arteriosclerosis and hypertension.

In vivo hypotensive effect may be partly attributed to its inhibition of biosynthesis and release of arachidonic acid-derived vasoconstrictor products.

Baicalein may reduce vasoconstricting sensitivity to receptor-dependent agonists such as noradrenaline, phenylephrine.

inhibition of the endothelial nitric oxide-dependent mechanism.

anti-thrombotic

Baicalein inhibits thrombin-induced production of plasminogen activator inhibitor-1, and interleukin-1beta- and tumor necrosis factor-alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells.

Anti-ischemia-reperfusion injury in cardiomyocytes..

The free radical scavenging capacity When flavonoids were administered during

ischemia/reperfusion, baicalein significantly reduced cell death.

Anti-atherosclerosis

Atherosclerosis is a multiple factors disease, in which the main roles play oxidant stress, endothelium dysfunction and disorders of hemostasis

Hangqin in the nearest future could be used in the primary and secondary prevention of atherosclerosis

Mechanism: anti-oxidant, increase HDL and reduces TG et al.

Qing Hao(http://www.who.int/mediacentre/factsheets/fs094/en/index.html)

II. WHO RECOMMENDATIONS ON MALARIA TREATMENT

antimalarial medicines, WHO recommends that all countries experiencing resistance to conventional monotherapies, such as chloroquine, amodiaquine or sulfadoxine yrimethamine, should use combination therapies, preferably those containing artemisinin derivatives (ACTs artemisinin-based combination therapies) for falciparum malaria (3, 4).

Forms of artemisinin, developed in China from the wormwood plant, have become the leading treatment — but only when used together with older medications. This artemisinin combination therapy, known as ACT is 95 percent effective in curing malaria.

1. Antimalarial: The mechanism is associated with the blocked utilization of host erythrocyte protein by the plasmodium, causing starvation and death.

2. Antibiotic: It can inhibit Staphylococcus aureus, Neisserria catarrhalis.

3. Antihypertensive: It can decrease ht rate, inhibite contraction of the cardic muscle.

4. Antipyretic:

5. Cholagogic: it can increase the production & excretion of bile in rates.

WHO currently recommends the following combination therapies (in alphabetical order):

1. artemether/lumefantrine 2. artesunate plus amodiaquine (In areas where the cure rate of

amodiaquine monotherapy is greater than 80%) 3. artesunate plus mefloquine (Insufficient safety data to

recommend its use in Africa) 4. artesunate plus sulfadoxine/pyrimethamine (In areas where the

cure rate of sulfadoxine/pyrimethamine is greater than 80%) Note: Amodiaquine plus sulfadoxinepyrimethamine may be

considered as an interim option where ACTs cannot be made available, provided that efficacy of both is high.

Zhi Mu (Radix Anemarrhence)[Main Components]Timosaponin, mangiferin, sarssapogenin.

[Effects and HTCM]1. Anti-microbes: It has effect against Staphylococcus aureus,

αand β-hemolytic strepcholerace, Salmonella typhi, E.coli, Bacillus subtilis.

2. Antidiabetic:

3. Anti-pyretic (abate fever): It has a slow onset but pronged duration.

[Interaction] Antidiabetics:

Coptis Detoxicating Decoction (Huang Lian Jie Du Tang)

[Ingredients]

1. Huang Lian (Coptis root) 9g

2. Huang Qin (Scutellaria root) 6g

3. Huang Bai (Phellodendron bark)6g

4. Zhi Zi (Capejasmine fruit) 6g

[Effects & HTCM] Purging fire and expelling toxin. Used for: fire toxin obstructing the three Jiaos.1. Anti-microbes and Anti-toxin(anti-bacillus dysenteriae)2. Anti-pyretic and sedating3. Effects on immune function4. Lower blood pressure Without Huang Lian in the formula , the blood pressure lowering

action is decreased. Without Huang Qin and Zhi Zi in the formula, the blood pressure

lowering action is increased.5. Promotes cerebral circulation. It can treat senile dementia

and dementia due to cerebral ischemia. 6. Anti-peptic ulcer. It can control the activity of hydrogen ions in

digestion.

[Indications]1. Septicemia, Pyotoxinemia2. Tonsillitis3. Hypertension4. Diseases of cerebral vessels5. Sequelae of wind stroke6. Alzeheimer’s disease 7. Herpes Zoster [Side Effects]  

Chapter 4 Herbs that purge  Properties of herbs that purge 1. Purging action (1)   Stimulate the movement of the intestine (Da Huang) (2)   Increase the water content of the intestine (Mang Xiao) (3)   Moisten the stool (Huo Ma Ren)2. Induce urination3. Anti-microbes, anti-toxin: Anti-amoebic dysentery4. Anti-inflammation Da Huang accomplished this by decreasing the

prostaglandin (PG)

5. Anti-cancer Da Huang can kill breast cancer cells by

means of restraining their protein synthesis   Examples of herbs that purge

Da Huang (Rhubarb)[Main Components]1. Anthraquinone (chief component for

purging)2. Glycoside3. Rhein4. Chrysophanol5. Emodin6. Acatechin7. Gallic acid

[Effects & HTCM]Purge heat to relieve constipation and clear gastrointestinal

tract as well as invigorating blood to remove stasis.1. Effects on digestive system(1)   Purging actions: stimulate intestinal movement.

However, it can cause constipation if it is decocted for a longer time because of tannic acid

(2)   Protect liver and cholagogize (benefit the gall bladder)

    a. It can help the gall bladder contract promoting bile secretion    b. It can lower serum cholesterol level c.It can prolong the life of liver cells and promote regeneration of

liver cells

 (1)   Stimulate pancreatic secretions and restrain the activity of pancreatic juices

TCM believes Da Huang is cold and bitter and will injure the stomach.

(2)   Anti-peptic ulcer a. It can control the activity of hydrogen ion in digestion b. It can prevent stress to ulcer by means of promoting the

PGE22. Effect on blood (1)   Stop bleeding The a-catechin and gallic acid can increase the adherence

of platelets. They can increase the contraction of blood vessels

(2) Reduce blood stasis

3.Promote the renal function (1)   It can lower the level of BUN and

Cholesterol and triglycerides. (2)   It has a remarkable suppressive effect on

the growth of both the renal tubules and the mesangial cells in vitro by suppressing the production of TNF and IL-1.

    4. Anti-infection(1)   The rhein, chrysophanol, emodin can suppress bacteria and virus(2)   Anti-pyretic and sedating actions(3)   Effects on immune function 5.Anti-cancerRhein, chrysophanol, emodin, a-catechin and gallic acid can suppress the RNA and DNA synthesis of cancer cells.

[Indications]

1. Constipation

2. Bleeding: Ulcer hematemesis

3. Dysentery and Acute Enteritis

4. Acute Abdominal inflammation (Pancreatitis, Peritonitis)

5. Renal failure

6. Hyperlipidemia

[Side Effects]1. It causes pathologic changes in liver and thyroid with hypertrophy of

tissue cells.

2. Common adverse effects: nausea, vomiting, diarrhea, and abdominal pain.

3. Drug interaction: prolonged use of Da Huang may cause loss of potassium, leading to increased toxicity of cardiac glycosides, such as digoxin.

Da Cheng Qi Decoction (Major Order the Qi Decoction)

[Ingredients]

1. Da Huang (Rhubarb) 12g

2. Mang Xiao (Mirabilite) 9g

3. Hou Po (Magnolia) 12g

4. Zhi Shi (Unripened bitter orange) 9g

Used for: Yang Ming fu-organ disorder with dry stool in the

intestines [Effects & HTCM]1. Purging actions2. Effects on intestinal obstruction. It can promote

the circulation of vessels of the intestines, decrease blood deficiency in the intestines, and help the intestines to regain function after surgery.

3. Anti-bacterial. (both gram-positive and gram-negative bacteria)

[Indications] [Side Effects]

Chapter 5 Herbs that expel dampness1. Gastrointestinal: To increase peristalsis of the intestines and

production of gastric acid.

2. Antibiotic: Huo Xiang, Cang Zhu, Hou Po, Sha Ren have effects against Viruses and bacteria.

3. Antiulcer:

Medicinal UsesDisclaimer Antibacterial; Carminative; Expectorant; Homeopathy;

Stimulant. The fruit is antibacterial, carminative, diuretic, odontalgic, stimulant,

and stomachic[4, 21, 61, 176, 240]. It is taken internally in the treatment of abdominal pain, digestive disturbances and complaints such as lumbago[176, 238]. It is often included in remedies for digestive disturbances and cough mixtures, in part at least for its pleasant aniseed flavour[238]. An effective remedy for various digestive upsets, including colic, it can be safely given to children[254]. The fruit is also often chewed in small quantities after meals in order to promote digestion and to sweeten the breath[4, 238]. The fruit has an antibacterial affect similar to penicillin[176]. The fruit is harvested unripe when used for chewing, the ripe fruits being used to extract essential oil and are dried for use in decoctions and powders[238]. A homeopathic remedy is prepared from the seed[4].

 Nat Cell Biol. 1999;May:1(1):60

Indirubin(Dian Yu Hong), the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases.

Hoessel R, Leclerc S, Endicott JA, Nobel ME, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, Niederberger E, Tang W, Eisenbrand G, Meijer L.

Department of Chemistry, University of Kaiserslautern, Germany.

Indirubin is the active ingredient of Danggui Longhui Wan, a mixture of plants that is used in traditional Chinese medicine to treat chronic diseases. Here we identify indirubin and its analogues as potent inhibitors of cyclin-dependent kinases (CDKs). The crystal structure of CDK2 in complex with indirubin derivatives shows that indirubin interacts with the kinase's ATP-binding site through van der Waals interactions and three hydrogen bonds. Indirubin-3'-monoxime inhibits the proliferation of a large range of cells, mainly through arresting the cells in the G2/M phase of the cell cycle. These results have implications for therapeutic optimization of indigoids.

Example of herbs that expel dampness   Huo Xiang Zheng Qi San (Agastache powder

to rectify the qi) [Ingredients]1. Hou Po (Magnolia Officinalis) [Components] essential oil and some alkaloids2. Huo Xiang (Pogostemon Cablin) [Components] essential oil, patchouli alcohol,

and pogostone

[Effects & HTCM]1. Regulate the function of the stomach and intestines (1)   Relax intestinal spasm (2)   Low dosage can stimulate movement of stomach

and intestines 2. Promote the digestive function. It can help the

intestines absorb sugar and water3. Analgesia. It can stop the pain caused by heat in

rats.4. Increase the immune function. It can increase the

lymphocytes in the blood and help injured intestines to recover.

5. Anti-bacterial. It can suppress Staphylococcus aureus, Typhoid, Bacillus, Bacillus dysenteriae.

[Indications]

1. Stomach flu

2. Acute gastroenteriris, acute colitis [Side Effects] Huo Xiang Zheng Qi Shui can cause drug

rash. When herb intake is discontinued, the rash will disappear.

Dan Shen

Dan shen

The dried root of Salvia miltiorrhiza A commonly used traditional Chinese

medicine to improve circulation and improve blood flow

Used for treating cardiovascular diseases such as coronary heart disease, hyperlipidemia and cerebrovascular disease

Chemical constituents

Lipophilic and hydrophilic compounds Lipophilic:Tanshinone analogues

(tanshinone IIA et al.) Hydrophilic: Salvianolic acids, danshensu

et al.

Pharmacokinetics

Major components absorbed rapidly after oral administration

Metabolized extensively by liver Excreted from stool and urine, Some components have low short half life,

low bioavailability, because of extensive metabolism

Danshensu

Dilates coronary arteries, Inhibit platelet aggregation Improve microcirculation Protect the myocardium from reperfusion

injury

Danshensu

The mechanism - prevent intracellular calcium increase - remove oxygen free radicals - Inhibit myocardial cell apoptosis - protect the endothelial cells against

homocysteinemia (risk factor for cardiovascular diseases and atherosclerosis)

Salvianolic acid B

Protect the brain from ischemia-reperfusion injury

Inhibit platelet aggregation Prevent low density lipoprotein (LDL),

uptake by cells Stimulate nitric oxide production by

endothelial cells Remove free radicals

Tanshinone IIA

Free radical scavenger property Also inhibition of angiotensin II activity,

attenuating cardiac cell hypertrophy

Angina

The commonest herb used to treat angina Improve microcirculation Induce coronary vaso-dilation Inhibit platelet adhesion and aggregation Suppressing thromboxane formation

Angina

Sublingual nitroglycerin is the gold standard for acute angina attacks

Provide an exogenous source of vasodilator- nitric oxide

Induce coronary and peripheral vasodilation

Prolonged nitrate therapy inhibit endothelium nitric oxide synthase – cause nitrate tolerance

Nitrate therapy

Vasodilatory effects

Reduce oxygen demand

Angina

Several research suggests that danshen is more suitable than isosorbide dinitrate in long-term treatment for angina

And suggests danshen is more effective than nitrates in the improvement of symptoms and ECG tests

Angina

Plus, increased platelet aggregation occurs in patients with angina, which can reduce the effect of nitrates therapeutic

The development of tolerance to nitrate therapy

More therapeutic activities

Coronary artery spasm Myocardial infarction - opening and formation of coronary

collateral circulation - additionally, has sedative, antioxidant,

antiplatelet, and improve microcirculation effects

Hyperlipidemia

Reduce total cholesterol and LDL, which are risk factors for coronary atherosclerosis

Protect endothelial cells from homocysteine-induced injury

Hypertension

Inhibit angiotensin converting enzyme and directly inhibit angiotensin II action

Reduce blood viscosity As a complementary therapy for

pregnancy induced hypertension Reduce incidence of arrhythmia

Peripheral vascular disease

Dilate peripheral vascular - reduce smooth muscle contraction - stimulate vascular dilating molecular

production Pulmonary vascular disease, protection

against pulmonary thromboembolism Improve vascular disease of diabetes

patience

Renal disease

Renoprotective effects Help for recovery of renal function in the

early stage of renal transplantation Reduce blood viscosity, p;atelet

aggregation and free radicals et al,

Side effects

No major side effects May hypotension, dizziness, drowsiness,

abdominal discomfort, decrease appetite and itching..

LD50 of water soluble extract was almost 4000 times higher in mice than the clinical human oral dosage

Dan shen

Numerous forms of Danshen are available in China

Fufang Danshen (with Panax notoginseng, Cinnamomum camphora)

Has been registered as a drug in several countries

And was the first TCM product approved by FDA for phase II and phase III clinical trials

Drug interaction

Warfarin Potentiate the anticoagulant action-

bleeding Increase the half life (CYP 450) Avoid patient taking warfarin

Drug interaction

Most drugs are bound to serum proteins to a various degree.

Only unbound or free drug is pharmacologically active.

under certain conditions, the equilibrium is disturbed and the measured free drug concentration can be significantly, especially for strongly protein-bound drugs.

In such case a patient may experience drug toxicity even if the total drug concentration is within the therapeutic range.

Drug interaction

Danshen (50-70%) strongly bind to protein Albumin as the major serum protein that

binds Danshen. Salicylate, which is also strongly bound to

albumin, is a widely used over-the-counter medicine in the U.S.

Digoxin

More

Reduces alcohol intake in alcohol- preferring rats

Hamper alcohol absorption from GI track without affect the severity of alcohol withdrawal syndrome in rats

Sanqi (Panax notoginseng)

Sanqi

The root of Panax Notoginseng It is the largest ingredient in 云南白药 (Yunnan

Bai Yao), a famous hemostatic herbal remedy Sweet and slightly bitter in taste, and nontoxic. The dose in decoction for clinical use is 5-10 g.

It can be ground to powder for swallowing directly or taking mixed with water: the dose in that case is usually is 1-3 grams.

Sanqi

Hemostatic effect Cardiovascular effect Protect the liver Anti-inflammatory effects Anti-carcinogenic effects on some forms of

cancer.

Sanqi

Contains many chemical constituents. Saponins derivatives (PNS), which is a

mixture of more than 20 types of saponins, four or five of them are considered as the principle active ones Notoginenoside R1, ginsenoside Rg1, Rd, Re

and Rb1 (75-80% total PNS) Flavonoids et al.

Pharmacokinetics

Oral administration, most Saponins derivatives (powder) tested in rats, reached peak concentration in plasma rapidly within about 0.75 h - hint their absorption were quick.

Maximum concentration in rat plasma were low indicated that it may be poorly absorbed and /

or extensive metabolized (intestinal microflora, liver) ….

Pharmacokinetics

Half time was changed from 1 to 20 hrs in rat plasma after oral administration of the constituents

Iv in rats, most constituents were cleared quickly except a couple of PNS the pharmacokinetic profile diversities of these

constituents are probably one of the mechanisms of the multiple pharmacology activities

San-qi

Many preparation were used in clinic in China (tablet, drop pill and injection)

Xuesaitong injection is consisted with only PNS Very difficult to evaluate the pharmacokinetic

profile Pharmacokinetics parameters are different

from individual compounds

San-qi Hemostatic effect

San-qi and a saponin (PNS) extract provide hemostatic effects. External application reduces bleeding time

The effect lost significantly after heating

Sanqi

Combination with Salvia miltiorrhiza (Danshen) and Ligusticum (Chuanxiong) efficaciously reduces lipoperoxidative damage to tissues

Thrombogenicity effects

PNS reduces platelet activation, adhesion and aggregation

Prevent thrombosis and improve microcirculation in patients with blood hyperviscosicity syndrome

Thrombogenicity effects

PNS iv or oral 200 mg/kg need 20 days to appear hint a slow effect compare to hemostatic

Fibrinolytic effects

Sanqi (the extract as notoginsenoside R1) increased the fibrnolytic potential in in vivo lab test, which may be beneficial to cardiovascular disease

Cardiovascular effects

Dilate the coronary artery Increase coronary blood flow, providing

more blood to the heart muscle Improves micro-circulation in and around

damaged heart tissue Reduces cardiac load, lowers arterial

pressure

Cardiovascular

Decrease the size of myocardial infarction Anti-arrhythmia PNS increases PGI2 and reduces

thromboxane A2 in platelets – correct the unbalance between the two prostaglandins

Anti-atherosclerotic effect

It helps lower cholesterol and triglycerides, to prevent the progression of atherosclerotic lesion

Effects on brain

Protect ischaemic brain damage Decrease brain edema, infarct size and

neuron damage Inhibit uptake calcium by neuron cells

isolated from rats Protect cultured rat cortical neuron from

glutamate neurotoxicity

Ischemic cascade1. Lack of oxygen causes the neuron's normal process for making ATP for energy to fail. 2. The cell switches to anaerobic metabolism, producing lactic acid. 3. ATP-reliant ion transport pumps fail, causing the cell to become depolarized, allowing ions, including calcium (Ca+

+), to flow into the cell. 4. The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high. 5. The presence of calcium triggers the release of the excitatory amino acid neurotransmitter glutamate. 6. Glutamate stimulates AMPA receptors and Ca++-permeable NMDA receptors, which open to allow more calcium

into cells. 7. Excess calcium entry overexcites cells and causes the generation of harmful chemicals like free radicals,

reactive oxygen species and calcium-dependent enzymes such as calpain, endonucleases, ATPases, and phospholipases in a process called excitotoxicity.[5][6] Calcium can also cause the release of more glutamate.

8. As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.

9. Mitochondria break down, releasing toxins and apoptotic factors into the cell. 10. The caspase-dependent apoptosis cascade is initiated, causing cells to "commit suicide." 11. If the cell dies through necrosis, it releases glutamate and toxic chemicals into the environment around it. Toxins

poison nearby neurons, and glutamate can overexcite them. 12. If and when the brain is reperfused, a number of factors lead to reperfusion injury. 13. An inflammatory response is mounted, and phagocytic cells engulf damaged but still viable tissue. 14. Harmful chemicals damage the blood brain barrier. 15. Cerebral edema (swelling of the brain) occurs due to leakage of large molecules like albumins from blood vessels

through the damaged blood brain barrier. These large molecules pull water into the brain tissue after them by osmosis. This "vasogenic edema" causes compression of and damage to brain tissue.

The fact that the ischemic cascade involves a number of steps has led doctors to suspect that neuroprotectants such as calcium channel blockers or glutamate antagonists could be produced to interrupt the cascade at a single one of the steps, blocking the downstream effects. Though initial trials for such neuroprotective drugs led many to be hopeful, until recently, human clinical trials with neuroprotectants such as NMDA receptor antagonists were unsuccessful.

Basic mechanism of excitotoxicity of stroke

It is widely believed that calcium entry into neurons significantly contributes to ischemia related toxicity remove Ca in experimental setting greatly

reduced hypoxic damage to neuron

Therapeutic strategy

Restore blood supply Minimizing Ca influx into cells Reducing free radical damage Promoting neural recovery

Tumor Radio-sensitivity

Taiwanese scientists studied the sensitization effect of Panax notoginseng extract and purified Saponin (Rb1) on the radiation response of an experimental tumor (KHT sarcoma) in comparison with its effects on a normal tissue (bone marrow) in mice

Tumor Radiosensitivity

Panax notoginseng extract at a concentration of 0.1-100 mg/kg produced an increase in tumor radiosensitivity.

Rb1 at a concentration 0.001 to 1 mg/kg produced an increase in tumor radiosensitivity, with maximum effect at 1 mg/kg.

The effect was maximal at 10 mg/kg and at 30 minutes after injection.

Higher doses of notoginseng (not Rb1) were toxic to the bone marrow stem cells

Further purified or synthetic versions are useful in cancer therapy.

Toxicity

Low Esophagitis from consuming tablets (drink

enough water) may occur Allergic reactions including dermatitis,

shock, purpura, blisters, or other idiosyncratic reactions

Chapter 6 Herbs that tonify   Properties of herbs that tonify:  1. Effects on the immune function (1)   It can increase the WBC and prevent the

decrease of WBC caused by chemotherapy (2)   It can promote the phagocytic function of

phagocytes (3)   It can build the function of Th cells (4)   It can regulate or help body produce IgG, IgA,

and SIgA

2. Effects on the nervous system: (1)   Regulate the function of cerebral cortex

( Ginseng, Huangqi) (2)   Excite the nervous function (Ginseng, Lu

Rong) (3)   Promote the circulation of the brain (Dang Gui) (4)   Components of the herbs are rich in proteins,

vitamins, and trace elements which can nourish the cerebral cells, promote the development of the brain, prevent cerebral senility.

3. Promote endocrine functions There are degenerations or atrophies of endocrine organs in most

of the deficient syndromes. (1) Promote the functions of hypothalamus-pituitary gland-

adrenal gland. Ginseng, Huang qi and Wu Jia Pi can stimulate the hypothalamus

and pituitary gland to secrete ACTH which in turn increases the cAMP (cyclic adrenosine monophosphate) of the adrenal gland and help it to synthesize cortical hormone.

(2) Excite the thalamus-pituitary gland-sexual gland Yin Yang Huo, Gou Qi Zi can excite them and promote the

secretion of sexual hormone. (3)   Excite the thalamus-pituitary gland-thyroid gland Some formulas that tonify yang (You Gui Wan) can stimulate

thyroid functions.

4. Effect on the cardiovascular system (1)   Ren Shen, Huang Qi, Mai Men Dong, Sheng Mai

San, Shen Fu Tang can promote function of the heart. (2)   Dang Gui, Yin Yang Huo, Mai Men Dong can

dilate coronary artery, promote the circulation of the coronary artery, and treat myocardial ischemia.

(3)   Dang Gui, shu di Huang, Liu Wei Di Huang Wan can lower blood pressure.

(4)   Si Jun Zi Tang, Sheng Mai San, Shen Fu Tong increase the blood pressure.

5. Promote the hematopoietic function Dang Shen, Dang Gui et al. can increase RBC by

stimulating the hematopoietic function of bone marrow.

6. Effects on the digestive system Dang Shen, Bai Zhu, Si Jun Zi Tong relax

intestinal spasm, and regulate intestinal movement , anti-peptic ulcer.

7.Prolong life (1)  Ren Shen, Huang Qi can prolong animal

cell’s life. (2)  Yin Yang Huo can stimulate the function

of SOD (superoxide dismutase)   Examples of herbs that tonify

Ren Shen (Ginseng) “Huang lian doesn’t get credit for curing diseases,

and Ren Shen doesn’t get punished even if it kills the patient”.

[Main Components]1. Volatile oil (0.05%)2. saponins, known as panaxosides or

ginsenosides3. antioxidants4. peptides5. polysaccharides fatty acids

[Effects & HTCM]1. Effects on central nervous system:

It has a stimulating effects in low doses, but an inhibiting effect in large doses. It increases the amounts of dopamine and norrepinephrine in the brain stem.

2. cognitive: improve memory and learning ability.

3.Endocrinological: it stimulates pituitary gland to increase the secretion of ACTH.

4. Immunostimulant:

5: cardiovascular:

6. Hypoglycemic:

7. reproductive:

2. Anti-cancer activity (1)   It can inhibit several types of cancer cell

growth in vitro (2)   Mice innoculated with S-180 cancer cells

survive for a longer time if given ginsenosides. (3)   Has the ability to inhibit the adhesion and

invasion of tumor cells in the lungs primarily due to their antiangiogenesis activity.

3.Anti –shock

[Indications]1. Arrythmia: for atrial fibrillation, sick sinus

syndrome, ventricular arrhythmia. 2. Angina pectoris3. Leukopenia4. Hepatitis5. Cancer6. Diabetes7. Prolonged life [Side Effects] It could cause eruptions, itching, headache, dizziness,

and body temperature increase as well as bleeding. It is prohibited in excessive syndromes, and damp-heat syndromes.

Huang Qi ( Astragalus Membranaceus) It is sweet, slightly warm. Enters Lung and

spleen. Tonify qi and stabilze exterior, promote urination and reduce edema, promote the discharge of pus and generate the flesh.

[Main Components]

1. Carbohydrates of astragalus

2. Glycoside

3. Alkaloids

4. amino acids, et al.

[Effects & HTCM]

1. Effects on the immune function (1)   It can increase the WBC and prevent the decrease of

WBC caused by chemotherapy. (2)   It can promote the phagocytic function of

phagocytes (3)   It can build the function of helper T lymphocytes

(Th cells) (4)   IT can regularte or help body produce IgG, IgA,

SIgA (5)   It can stimulate the lymphocyte activating factor

   2. Prolong life Huang Qi can prolong the animal cell’s life. (1)   It can stimulate the function of SOD (superoxide

dismutase) (2)   It can decrease free radicals (3)   It can increase catecholamine (CA), it inhibits the

activity of MAO-B3.Effects on the cardiovascular system (1)   It can promote function of the heart, especially

heart failure due to toxicity or fatigue.

(2)   Dilate blood vessels a.      It can dilate the peripheral vessels, cerebral

vessels, renal vessels, and coronary vessels as well as intestinal vessels. However, if the dosage of Huang Qi is too high, the renal vessels will be contracted due to a decrease of blood pressure

b.      It can promote the microcirculation, strengthen the defensive function of micro vessels, and prevent permeability of micro vessels caused by other diseases

(3)   It can lower the blood pressure

4. Effects on the hematopoietic function (1)   Promote the hematopoietic function It can increase the RBC and WBC by stimulating the

hematopoietic function of the bone marrow. (2)   Inhibit the aggregation of thrombocytes by

means of cAMP of thrombocytes

5. Effects on substance metabolism [Indications] [Side Effects]  

Question?

1. General speaking, which of the following group herbs they are mainly rich in alkaloid, and glycoside which posse anti-bacteium, Viral and inflammation ?.

A. sweet herbs

B. bitter herbs

C. sour herbs

D. salty herbs

2. The pungent herbs have the following actions except

A. relieving exterior syndrome: B. relaxing spasm C. relieving pain D. strengthening Qi and blood

3. The following herbs(aristolochic acid) have side effects on the kidney except

A. Mu tong

B. Han fang ji C. Chai Hu D. Ma duo Ling

4. What kinds of side-effects does the Ma Huang have?

A.lead to bleeding of eyes, increasing the

blood pressure B.exciting central nervous system C.lead to restlessness, insomnia. D. All A, B, C

5. Gui Zhi (Cinnamon twig, cinnamomun ) has the following actions except

A. dilating Blood-vessels to promote sweating

B. relieving asthma C. Reducing fever & stopping pain. D. Tranquilizing

1. According to the recent research of herbal pharmacology, Ge Gen (Kudzu, pueraria) not only can be used for reducing fever, relaxing the smooth muscle of intestine, but also for treating

A. diseases of lungs B. diseases of kidney C. diseases of digestion D. diseases of circulation system.

2. General speaking, the Herbs that clear heat syndrome have the following actions except

A.Anti-microrganism, Anti-toxinB.Effects on immunologic function C. Reducing edema

D. anti-cancer

3.Huang Lian(coptis root) is mainly used for acute enteritis and A. urinary tract infection B. Dysentery C. promote platelet adhesion D. disorder of the bacterium in intestine

4. What is the main side effect of the Huang Lian, if oral taking.

A.Few of them suffers from allergic reaction.B.reactions of gastric-intestine.C.reactions of the heartD.reactions of the respiration

5.Chai Hu(Bupleurum Root) is mainly used for the following diseases except

A. infective diseases

B. disorders of immunologic function

C. Diseases of digestion

D. diseases of hemapopoietic system

Questions?1.Coptis Detoxicating Decoction(Huang Lian Jie Du Tang) is good for A. stopping paing B. Anti-microrganism and Anti-toxin C. increasing blood pressure D. promoting the intestinal movement

2. Purging action of Mang Xiao is by means of A. stimulating the movement of the intestine B. increasing the water of the intestine C. moistening the intestine D. Decreasing the water of the intestine

3. The component of Da Huang(rhubarb) for purging is

A. anthraquinone B. emodin, C. a-catechin D. gallic acid.

5.Da Huang can promote the renal function by means of the following mechanisms except

A. lowing the level of BUN B. lowing Cholesterol and triglyceride. C. regulating cardiac functions D. suppressiving effect on the growth of both

renal tubules and messangial cells6. Da Huang can be used for A. constipation B. Renal failure C. Dysentery and Acute enteritis. D. All of A, B and C

7. The Da Huang has the following main Side-effect possibly except ?

A. it causes pathologic changes in liver and thyroid with hypertropy of the tissue cells.

B. it leads to bleeding

C. it causes nausea, vomiting

D. it causes abdominal pain.

Si Jun Zi Tang(Four Gentlemen Decoction) [Effects] 1. Effect on intestine: mainly inhibit the movement of

intestine. 2. Effects on the immune function: (1) It can prevent decreased phagocytic function caused by

cyclophosphamide or prednisone. (2) It can regulate or help body product IgG, IgA. (3) It can stimulate the lymphocyte activating factor.

3. Promote the hematopoietic function

(1) It can increase the RBC by means of stimulate the hematopoietic function of bone marrow.

4. It has the ability to inhibit the adhesion and invasion of tumor cells in the lung

[Indications]

1. Chronic diarrhea, ulcer,gastritis.

2. Chronic hepatitis

Liu Wei Di Huang WanIt can nourish yin and tonify kidney.

[Effects] 1. Promote the immune function(1) It can promte the weight of immune organs and

phagocytic function of phagocyte, functions of bone marrow which is decreased by cyclophosphamide or prednisone.

(2) Increase the function of phagocytic function of phagocyte.

(3) Stimulate the activity of C3b-receptor

2. Anti-cancers

(1) Reduce the incidence of cancers by means of preventing the halmatogenesis of normal cells and normal cells turning into cancer cells.

(2) The mechanism for anti-cancers has something with promoting immune function, but not due to killing cancer cells.

3. Promote hepatofunction and low blood lipid(1)low TC and fat in liver.(2)increase HDL-C and HDL-C/TC. Ze Xie and Mu Dan Pi are main herbs.4. Low blood sugar. Shan Zhu Yu, Mu Dan pi, Shan Yao, and Fu

Ling all can low blood sugar.5. Effect on calcium-phosphorus metabolism it can keep the calcium-phosphorus in

normal level, promote the calcium-phosphorus in the bone, so it can prevent the incidence of rickets.

6. Promote sexual function(1) Increase quantity of sperm(2) Increase the capacity of coitus(3) Increase the weight of sexual organs.

[indications]1. Diabetes2. Nephritis3. Chronic Prostatitis4. Climacteric syndrome5. Cancer6. Other diseases

Chapter 7. Herbs that warm interior The warming interior herbs have the

function of warming interior, dispersing cold, warming kidney meridian and restoring collapse yang.

Properties: Pungent and sweet in flavor, hot and toxic in nature; it is related to the heart, kidney and spleen channels.

Functions: Recuperating depleted yang and rescuing the patient from collapse, restoring yang and supplementing fire as well as dispersing cold and relieving pain.

1. Cardiovascular system: Fu Zi and Sini Tang (Fu Zi, Gan Jiang, Gan Cao) have the function of recuperating depleted yang and warming heart yang. Heart yang deficiency is similar to heart failure, and arrhythmia of slow irregular pulse. Studies have proven that Fu Zi, Wu Tou, Gan Jiang and Rou Gui have obviously functioned on cardiovascular system which is related to Fu Zi's DMC (dl-demethlcoclaurine).

(1) Promote cardiac contratility Function: Fu Zi can strengthen cardiac contraction, increase heart beat, increase cardiac output and increase cardiac muscle oxygen consumption volume. The main ingredient of

strengthening heart function in Fu Zi is believed to be DMC (dl-demethlcoclaurine) which relates to Beta receptor. If the Beta receptor is blocked, increased cardiac contraction and heart rate will noticeably be decreased. DMC can shorten the period between A to H wave, and there is no change between H and H to V wave. It can increase the inotropic cardiac conductivity. The pure extract of Gan Jiang proves to have direct excitant function on heart.

(2) Promote cardiac frequency and inotropic conductivity: Fu Zi is proven to have treatment effect on treating of arrhythmia with slow heart beat type. Also DMC and Shen Fu Tang have similar function, too.

(3) Dilate vessels and improve circulation: Fu Zi and Rou Gui can dilate coronary vessels, increase coronary circulation, improving cardiac circulation, dilate brain vessels, and increase brain vessel circulation.

(4) Anti-shock function: Collapse syndrome and minute pulse to almost no pulse condition are similar to shock in western medicine. Fu Zi, Sini Tang, Sheng Fu Tang can elevate arterial pressure to prolong animal's life due to hypovolemic shock (blood loss), septic shock (infection with endotoxin),

cardiogenic shock (myocardial infarct). And, it provides protection on shock due to lack of oxygen or narrowing the vessels.

2. Digestive function: Rou Gui and Wu Ju Yu are warm and pungent which benefits stomach. Jiang (ginger)'s aromatic and acrid function can stimulate oral and intestine membrane and improve local circulation which leads to increase stomach secretion, enzyme activity, increase digestion, increase appetite and disperse digestive stagnation. Wu Ju Yu and Gan Jiang also can stop vomiting.

3. CNS function: Fu Zi, Wu Tou, Hwa Jiao, Hu Jiao, Gan Jiang, Rou Gui can relieve pain at different level. Fu Zi, Wu Tou , Hwa Jiao have analgesic function. Some warm interior herbs also have tranquilizing function. Sini Tang can promote sympathetic nerve to promote heat and disperse cold.

4. Anti-infection, immune function : Fu Zi, Xi Sin can reduce inflammation due to enzyme, PE2, etc. in the animal testing. Fu Zi can promote immunity by increasing IgM or IgG.

Fu Zi (Prepared Aconite Root)  Two types: It is from the root of Wu Tou.

There are two types: Chuan Wu and Cao Wu.   Properties: Pungent and sweet in flavor,

hot and toxic in nature, it is related to the heart, kidney and spleen channels.It is the root of Chuan Wu and Cao Wu.

Modern Researches: This herb contains aconitine, hypaconitine, talastisamine, chuanwu base A, chuanwu base A, racemic norcoclaurine, coryneine, etc.

Monkshood root and its decoction have an obvious cardiotonic effect and prepared sliced monkshood root has a more powerful cardiotonic effect. The longer monkshood root is decocted, the more remarkable are its cardiotonic effects and the lower its toxicity. Its

cardiotonic effects are closely related to the racemic norcoclaurine contained therein. It has obvious anti-inflammatory effects on formol and protein arthritis. Both the hypaconitine and aconine that it contains have tranquilizing and analgesic effects. It can resist myocardial ischemia and hypoxia, stimulate the pituitary adrenocortical system and promote blood coagulation.

Functions: 1. Cardiac vascular system function: (1)Strength heart system (2)Antiarrhythmia (3)Dilate vessels, lower blood pressure (dl-

demethylcoclaurine, higenamine), (4)increase blood pressure (coryneine

chroiole and salsolinol, SAL) (5)Protect heart muscle, promote enduring

time of lacking oxygen.

(6)  Anti-shock 2. CNS system function: (1) Anti cold (2) Relieve pain (3) Analgesia 3. Anti-infection, increase immunity: (1)Anti-infection (2)Increase immune function 4. Others: (1) Digestive function (2) Increase Beta receptor, cAMP system reaction

   (3)Increase KPTT and PCT time ( Fu Zi's activating blood function).

 Indications: 1. Shock 2. Cardiac disorder (arrhythmia) 3. Arthritis, joint pain, lumbar pain, etc.   Cautions: Being pungent, hot, dry and drastic, this

drug should be avoided by anyone with hyperactivity of yang due to yin deficiency or by pregnant women. It is against pinellia tuber,

Mongolian snakegourd (Fructus Trichosanthis), fritillary bulb (Bulbus Fritillariae Thunbergii), Japanese ampelopsis (Radix Ampelopsis) and hyacinth bletilla tuber (Rhizoma Bletillae). Being toxic, it should be blast-fried for oral administration. Any excessive oral administration or any improper blast-frying or decocting way may lead to poisoning.

Thank You